The goal of this renewal application is to enhance and expand our ability to elucidate causes of and identify potential treatments for such devastating neurological disorders as Alzheimer's and Parkinson's disease, and epilepsy by focusing our Center of Biomedical Research Excellence (COBRE) on the "Pathophysiological Signaling in Neurodegenerative Diseases". Using molecular/genetic, pharmacological, electrophysiological, biochemical and systems biology approaches we have proposed five projects that study the involvement of such signaling systems as ion channels and receptors, second messengers especially those lipid-based, subcellular organelles, gene transcription and protein translation in various model systems for neurodegenerative diseases. Our long term goal is to develop and support a scalable and sustainable group of neuroscience researchers who are focused to determine mechanisms causing, and to discover novel strategies to prevent and treat neurodegenerative diseases. This group will continue to be highly interactive and collaborative and will continue to play a role critical to leading UNO through its culture change as it approaches its goal of becoming a highest-level Carnegie research-based academic institution. Our specific aims are: (1) Support successful independent research projects and increase the competitiveness of our COBRE investigators for extramural grants through extensive mentorship and by funding five research projects and smaller pilot grants. (2) Enhance the research infrastructure at UNO by increasing our support for our COBRE core facilities. This will be accomplished by covering the costs of service contracts and salaries for technical personnel. (3) Increase our competitiveness by hiring at least two new neuroscience faculty members. UNO will support the further development of this group by hiring additional faculty that will enhance our capabilities in the areas of molecular/genetics and/or proteomics. (4) Establish our nationally and internationally recognized Center of Neuroscience Research Excellence under the auspices of a much larger Red River Neuroscience Initiative/Institute. Successful competition for this continuing renewal will ensure the success of this group receiving individual, group and training grants because we enjoy the support of UNO administration, we have been successful, our science is outstanding and all indicators suggest that our group is both scalable and sustainable.